Registry Study of Revcovi Treatment in Patients With ADA-SCID

Single Arm, Open-Label, Multicenter, Registry Study of Revcovi (Elapegademase-lvlr) Treatment in ADA-SCID Patients Requiring Enzyme Replacement Therapy

This registry study is being conducted in patients with adenosine deaminase severe combined immune deficiency (ADA-SCID) who require enzyme replacement therapy (ERT) treatment with Revcovi. Data on safety and on measures of efficacy are collected.

Study Overview

• Status: Completed
• Conditions: Adenosine Deaminase Severe Combined Immunodeficiency
• Intervention / Treatment: Biological: elapegademase-lvlr

Detailed Description

Patients with ADA-SCID who require ERT will receive Revcovi on a dosage and schedule determined by the treating physician. They will be followed for safety throughout the study, and will be monitored for the efficacy markers of adenosine deaminase (ADA) activity and deoxyadenosine nucleotide (dAXP) concentration according to a suggested schedule. Some subjects will be new to ERT; some will have transitioned from Adagen, which was the ERT available before Revcovi; and some will have previously participated in an earlier Phase 3 trial of Revcovi (study STP-2279-002). Patients will be followed either until they are able to successfully undergo a stem cell transplant or stem cell gene therapy and thus no longer require ERT treatment, or until all ongoing participants have received a minimum of 24 months of Revcovi treatment.

Note: Due to the nature of this study, all analyses are descriptive and no statistical hypotheses will be tested.

• Study Type: Observational
• Enrollment (Actual): 32

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095-1752
      • University of California Los Angeles
    • San Diego, California, United States, 92123
      • Allergy & Asthma Medical Group and Research Center, A P.C.
    • San Francisco, California, United States, 94158
      • UCSF - University of California
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Children's National
  • Florida
    • Saint Petersburg, Florida, United States, 33701
      • University of South Florida Allergy Immunology Clinic
  • Louisiana
    • New Orleans, Louisiana, United States, 70118
      • Childrens Hospital of New Orleans
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • Children's Minnesota
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • St. Louis Children's Hospital - Washington University School of Medicine
  • New York
    • Buffalo, New York, United States, 14203
      • UBMD Pediatrics Outpatient Center
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke University Hospital
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Children's Hospital
    • Pittsburgh, Pennsylvania, United States, 15224
      • UPMC Children's Hospital of Pittsburgh
  • Tennessee
    • Memphis, Tennessee, United States, 38105
      • Le Bonheur Children's Hospital
  • Washington
    • Seattle, Washington, United States, 98101
      • Seattle Children's

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second to 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with ADA-SCID who require ERT

Description

Inclusion Criteria:

• Male or female, aged newborn to adult

• In need of ERT treatment due to one of the following circumstances:

  • Waiting to receive a stem cell transplant
  • Previously declined, had been found to be ineligible for, or did not respond to a stem cell transplant
  • Waiting to enrol in a clinical trial on gene therapy, or had been found to be ineligible for or had failed such a trial

• One of the following histories of ERT treatment:

  • Revcovi only
  • Previously on Adagen but had transitioned to Revcovi
  • Not yet on any ERT but about to start on Revcovi

Exclusion Criteria:

• Any condition that, in the opinion of the Investigator, makes the patient unsuitable for the study.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Other

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Patients with ADA-SCID in need of ERT treatment; All participants will receive Revcovi. For analysis purposes, there will be three groups, who differ with respect to ERT history: Adagen-naïve: Subjects starting on ERT for the first time; Adagen-transitioning: Subjects switching from Adagen to Revcovi; STP-2279-002 participants: Subjects who had taken part in an earlier Phase III trial of Revcovi (study STP-2279-002) in which they had been switched from Adagen to Revcovi. This last group differs from the Adagen-transitioning group in that they will have been on Revcovi the longest.

Biological: elapegademase-lvlr; Revcovi is administered intramuscularly (i.m.). Weekly dosage is calculated in mg/kg of body weight, and can be adjusted over the course of the trial based on ADA activity and dAXP concentration as well as on clinical assessment by the treating physician.; Other Names: Revcovi

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects Meeting the Toxicity Threshold for Deoxyadenosine Nucleotide (dAXP) Concentration at the Last Measurement	A deficiency in the ADA enzyme results in a build-up of dAXP nucleotides, which are toxic to lymphocytes and lead to impairment of immune function. A detoxified level of dAXP concentration is defined as a trough value of 0.02 millimoles per liter (mmol/L) or lower. Data are presented as the number of subjects who met the targeted threshold at the final measurement, whether that took place at Month 24 or earlier.	From enrollment to end of treatment up to Month 24
Number of Subjects Meeting the Optimal Threshold for ADA Activity at the Last Measurement	An optimal level of ADA plasma activity is defined as a trough value of 30 millimoles per hour per liter (mmol/h/L) or greater. Data are presented as the number of subjects who met the targeted threshold at the final measurement, whether that took place at Month 24 or earlier.	From enrollment to end of treatment up to Month 24
Safety of Revcovi	The number of subjects reporting adverse events (AEs). Due to the nature of ADA-SCID, only AEs deemed to be at least possibly related to Revcovi treatment were documented.	From enrollment to end of treatment up to Month 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immune status (SSA/PI)	Absolute lymphocyte count and subset B, T, and NK analysis. Immunoglobulin (Ig) concentrations (IgG, IgA, and IgM). Measurement of immune response at Investigator discretion.	Month 24
Clinical status	Infections (clinically or microbiologically documented) Incidence and duration of hospitalizations Growth for patients < 18 years old Overall survival through the end of study	Month 24
Safety assessed by determining adverse events (AEs), serious adverse events (SAEs)	Assessed by determining adverse events (AEs), serious adverse events (SAEs), clinical signs and symptoms from physical examinations, and laboratory examinations	Month 24

Collaborators and Investigators

• Sponsor: Chiesi Farmaceutici S.p.A.

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2019
• Primary Completion (Actual): January 18, 2023
• Study Completion (Actual): January 18, 2023

Study Registration Dates

• First Submitted: March 12, 2019
• First Submitted That Met QC Criteria: March 13, 2019
• First Posted (Actual): March 18, 2019

Study Record Updates

• Last Update Posted (Actual): November 15, 2024
• Last Update Submitted That Met QC Criteria: September 11, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: ADA-SCID; ERT; Revcovi
• Additional Relevant MeSH Terms: Primary Immunodeficiency Diseases; Genetic Diseases, Inborn; Metabolic Diseases; Immune System Diseases; Infant, Newborn, Diseases; Immunologic Deficiency Syndromes; DNA Repair-Deficiency Disorders; Severe Combined Immunodeficiency; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Adenosine Deaminase Inhibitors; Elapegademase
• Other Study ID Numbers: CLI-06814AA1-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No